The presence of circadian variation in the occurrence of unfavorable events has been demonstrated in several cardiovascular conditions, including elevations in blood pressure, ambulatory myocardial ischemia, onset of myocardial infarction, sudden cardiac death, and stroke. To investigate the mechanisms underlying the circadian variation in cardiovascular disease, we studied 12 nodal subjects with determinations of basal forearm vascular resistance and the response to intraarterial infusion of phentolamine (alpha-adrenergic blocker) and sodium nitroprusside (non-specific vasodilator) at 7:00 AM, 2:00 PM, and 9:00 PM. A circadian variation in basal forearm vascular resistance was observed, resistance being highest in the morning, and lower in the afternoon and evening. Reductions in forearm vascular resistance with phentolamine showed a similar circadian distribution; however, no such variation in the vasodilator response to sodium nitroprusside was observed. These findings indicate that circadian variation exists in vascular tone, with highest tone in the morning and lower in the afternoon and evening. This variation is determined by changes in alphasympathetic vasoconstrictor activity and may causally contribute to the higher blood pressure and increased incidence of cardiovascular events observed in the morning hours.